范科米的催化位点选择性硫基化和脱氧化显示出基依赖的形状效应
Brandon S Fowler1, Kai M Laemmerhold, Scott J Miller
1Department of Chemistry, Yale University, P.O. Box 208107, New Haven, Connecticut 06520-8107, USA.
Journal of the American Chemical Society
|May 25, 2012
概括
类催化剂被用于选择性选择性甲化,产生了两种新的脱氧-甲衍生物. 这些化合物揭示了令人惊的结构变化和改变的生物活动,突出显示了基基的结构作用.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 催化剂是一种催化剂.
背景情况:
- 范科米辛是治疗严重细菌感染的关键抗生素.
- 修改万科米辛可以克服耐药性并提高疗效.
- 选择性功能化是产生新型万科米辛类似物的关键.
研究的目的:
- 开发基于的催化剂,用于选择性地选择性地进行范科米的硫化.
- 为了合成新的脱氧-万科米辛衍生物.
- 为了研究脱氧化的结构和生物影响.
主要方法:
- 选和合理设计的类催化剂.
- 对受保护的万科米辛的选择性 thiocarbonylation.
- 关键中间体的扩大规模合成 (0.50g级) 的关键中间体.
- 脱氧反应以产生新的类似物.
- 规范分析和生物活性测试.
主要成果:
- 鉴定了可以增强或改变万科米二化选择性的类催化剂.
- 成功合成了两种新的脱氧-万科米辛衍生物.
- 在脱氧-万科米辛类似物中观察到意想不到的形状变化.
- 证明这些形状变化与改变的生物活动相关.
结论:
- 类催化剂为选择性菌素修饰提供了一种可行的策略.
- 范科米的脱氧可以导致显著的形状和功能变化.
- 特定的基团在原生万科米的活性中起着关键的结构性作用.
相关概念视频
02:34Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.
02:36Regioselectivity and Stereochemistry of Hydroboration
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
01:14Keto–Enol Tautomerism: Mechanism
The keto and enol forms are known as tautomers and they constantly interconvert (or tautomerize) between the two forms under acid or base catalyzed conditions. Both the reactions involve the same steps—protonation and deprotonation— although in the reverse order.
03:08Hydroboration-Oxidation of Alkenes
In addition to the oxymercuration–demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
01:35Loss of Carboxy Group as CO2: Decarboxylation of Malonic Acid Derivatives
Just like β-keto acids—which upon thermal decarboxylation form ketones—β-dicarboxylic acids undergo decarboxylation to generate monocarboxylic acids with the liberation of carbon dioxide.
01:22Reactions of Aldehydes and Ketones: Baeyer–Villiger Oxidation
Baeyer–Villiger oxidation converts aldehydes to carboxylic acids and ketones to esters. The reaction uses peroxy acids or peracids and is often catalyzed by acid. The reaction is named after its pioneers, Adolf von Baeyer and Victor Villiger. The reaction is achieved by a wide range of peracids such as m-chloroperoxybenzoic acid (mCPBA), perbenzoic acid (C6H5COOOH), peracetic acid (CH3COOOH), hydrogen peroxide (H2O2), and tert-butyl hydroperoxide (t-BuOOH).
The carbonyl center is activated by...
The carbonyl center is activated by...